Chia June A, Simms Lisa A, Cozzi Sarah-Jane, Young Joanne, Jass Jeremy R, Walsh Michael D, Spring Kevin J, Leggett Barbara A, Whitehall Vicki L J
The Conjoint Gastroenterology Laboratory, Royal Brisbane and Women's Hospital Foundation Clinical Research Centre and the Queensland Institute of Medical Research, Brisbane, 4029, Australia.
BMC Cancer. 2006 Oct 24;6:252. doi: 10.1186/1471-2407-6-252.
SnoN is an important regulator of the transforming growth factor beta (TGFbeta) signalling pathway and has been shown to exhibit both tumour promotion and suppression activity.
To further explore the role of this complex molecule in colorectal tumorigenesis, we examined 52 paired normal and tumour colorectal specimens stratified by level of microsatellite instability; 18 with high-level microsatellite instability (MSI-H) and 34 microsatellite stable (MSS). SnoN transcript expression was quantitated by real-time PCR and analysed with respect to clinical indicators of prognosis.
Within the MSI-H subgroup, SnoN was commonly either up-regulated (6/18, 33%) or down-regulated (7/18, 39%). A significantly different distribution of SnoN expression was observed in MSS cancers compared with MSI-H (P < or = 0.001). Whilst 17/34 (50%) of MSS tumours demonstrated up-regulation, none showed down-regulated expression. Within the MSI-H subgroup, up-regulation was significantly correlated with lack of repeat tract mutation in the TGFbetaRII gene (P < or = 0.025), suggesting that SnoN is more frequently up-regulated in the presence of functional TGFbeta signalling.
Together these data support the notion that SnoN has both oncogenic and tumour suppressive properties depending on other genetic changes within the tumour, and that the MSI-H pathway of colorectal tumorigenesis presents an excellent model for the study of these opposing functions.
SnoN是转化生长因子β（TGFβ）信号通路的重要调节因子，已显示出具有肿瘤促进和抑制活性。
为进一步探究这种复杂分子在结直肠癌发生中的作用，我们检测了52对根据微卫星不稳定性水平分层的正常和肿瘤性结直肠标本；其中18例为高度微卫星不稳定（MSI-H），34例为微卫星稳定（MSS）。通过实时PCR对SnoN转录本表达进行定量，并分析其与预后临床指标的关系。
在MSI-H亚组中，SnoN通常要么上调（6/18，33%）要么下调（7/18，39%）。与MSI-H相比，MSS癌中SnoN表达分布存在显著差异（P≤0.001）。虽然34例MSS肿瘤中有17例（50%）表现为上调，但无一例表现为下调。在MSI-H亚组中，上调与TGFβRII基因中无重复序列突变显著相关（P≤0.025），这表明在功能性TGFβ信号存在的情况下，SnoN更频繁地上调。
这些数据共同支持了这样一种观点，即SnoN根据肿瘤内的其他基因变化具有致癌和抑癌特性，并且结直肠癌发生的MSI-H途径为研究这些相反功能提供了一个极好的模型。
